Methods and apparatus for cleaning or disinfecting a water delivery system

ABSTRACT

Methods for cleaning or disinfecting water delivery systems, self-cleaning or self-disinfecting water delivery systems, and inserts for use in cleaning or disinfecting water delivery systems utilize cationic steroidal antimicrobial (CSA) molecules to kill microbes and/or break up biofilms within water delivery systems. The methods and systems involve adding CSA molecules to water to form an aqueous CSA composition and passing the aqueous CSA composition through the water delivery system, such as a water storage vessel and/or water delivery line to clean or disinfect the water delivery system. CSA molecules can be added to a water storage vessel, water delivery line, or well, such as by a solid or liquid CSA composition. A CSA-eluting composition may provide CSA molecules to water to form an aqueous CSA composition that passes through or is stored within the water delivery system. CSA molecules provided to agricultural animals in drinking water may improve animal health.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional PatentApplication No. 61/986,435, filed Apr. 30, 2014, and also U.S.Provisional Patent Application No. 62/009,523, filed Jun. 9, 2014, thedisclosures of which are incorporated herein in their entirety.

BACKGROUND OF THE INVENTION

1. The Field of the Invention

The invention relates to methods and apparatus for cleaning ordisinfecting water delivery systems, such as water delivery lines orwater storage vessels which provide drinking water to animals or humans.

2. the Relevant Technology

Clean and safe water for humans and animals is a valuable commodity.This is particularly true in the case of agricultural animals raised toprovide food for human consumption. Unclean water can cause or spreaddisease, which can harm both animals and those who consume animalproducts, such as meat, dairy products, and eggs. Avoiding disease isespecially important in the case of confined animal feed operations. Toavoid disease and also to improve animal health generally and induceweight gain, agricultural animals are often fed antibiotics.Unfortunately, antibiotics can be found in animals and animal products,making them less safe for human consumption.

The United States and other industrialized nations have extensive watersystems for delivering safe water to houses and business. Unfortunately,water for humans or animals is only as safe and clean as the storagevessels and water delivery lines that store and deliver such water. Toprevent disease, culinary water is often treated with chemicals such aschlorine to inhibit growth of bacteria and parasitic organisms.Unfortunately, chlorine can impart a bad taste and is harmful or toxicto humans or animals at higher concentrations. In addition, chlorine maynot be effective at preventing the formation of biofilms on interiorsurfaces of storage tanks and water lines. Nor does chlorine mitigatebad taste and potentially harmful effects of metals contained in water.

SUMMARY

Disclosed herein are methods for cleaning and disinfecting waterdelivery lines and systems using cationic steroidal antimicrobial (CSA)molecules. Also disclosed are self-cleaning or self-disinfecting waterdelivery systems that utilize CSA molecules and also CSA-eluting insertsfor attachment to and cleaning or disinfecting of a water deliverysystem by releasing CSA molecules. The CSA molecules introduced into awater deliver system can kill microbes and/or break up biofilms that maycontaminate a water delivery line or water storage vessel.

In some embodiments, a method for cleaning or disinfecting a waterdelivery line comprises: (1) adding cationic steroidal antimicrobial(CSA) molecules to water to form an aqueous CSA composition; and (2)passing the aqueous CSA composition through the water delivery line toclean or disinfect the water delivery line.

In some embodiments, a method for cleaning or disinfecting a waterdelivery system comprised of a water storage vessel or well and a waterdelivery line in fluid communication with the water storage vessel orwell comprises: (1) adding cationic steroidal antimicrobial (CSA)molecules to water to form an aqueous CSA composition; and (2) passingthe aqueous CSA composition through at least one of the water deliveryline or water storage vessel.

In some embodiments, a self-cleaning or self-disinfecting water deliverysystem, comprises: (1) at least one of a water delivery line or a waterstorage vessel; and (2) a CSA-releasing composition on an interiorsurface of the water delivery line and/or within the water storagevessel, wherein the CSA-releasing composition is formulated to releaseCSA molecules into water in the water delivery line and/or water storagevessel.

In some embodiments, a CSA-releasing insert for attachment to andcleaning or disinfecting of a water delivery system, comprises: (1) aninsert substrate for placement on or within a water storage vessel orwater delivery line; and (2) a CSA-eluting composition on a surface ofor impregnated in the insert substrate, wherein the CSA-elutingcomposition is formulated to release CSA molecules into water within awater storage vessel or water delivery line.

In some embodiments, the water delivery system provides drinking waterto animals, such as agricultural animals, examples of which includecattle, horses, sheep, swine, turkeys, and chickens. In someembodiments, the animals may be located at a confined animal feedoperation, and the CSA molecules are used to clean a water deliverysystem so as to prevent or slow the spread of disease. In addition tocleaning and disinfecting a water delivery system, CSA molecules, wheningested by animals, can improve the health of the animals. By way ofexample, not limitation, the CSA molecules can provide at least one ofthe following benefits: (1) reduced harmful bacteria in a digestivetract of an animal; (2) increased beneficial bacteria flora in thedigestive tract of the animal; (3) improved feed conversion efficiencyby the animal; (4) reduced morbity of the animal; (5) reduced mortalityof the animal; or (6) harvested meat from the animal having a reducedcontent of harmful bacteria.

In some cases, the aqueous CSA composition is formulated to break upbiofilms within the water line and/or form complexes with metal ions,metal compounds, or contaminants in water passing through the waterline. In some embodiments, the aqueous CSA composition is periodicallypassed through the water line, and water without CSA molecules is alsoperiodically passed through the water line.

In some embodiments, the water line may provide drinking water tohumans. In some cases, the water line may form part of a culinary watersystem which includes a water storage vessel or well containing waterand one or more water delivery lines in communication with the storagevessel or well that deliver water to one or more locations, such ashomes or businesses. The one or more water delivery lines may comprise aplurality of pipes or conduits, such as pipes or conduits made of metalor a polymer. The CSA molecules can be added directly to water in thestorage vessel or well and/or combined with water, liquid, or solid toform a concentrated CSA composition that is introduced into a storagevessel, well, and/or one or more water delivery lines.

In the case where CSA molecules form complexes with metal ions, metalcompounds, or contaminants, it may be desirable to filter the water toremove at least a portion of such complexes in order to yield purifiedwater. This can be accomplished using water filtration or purificationsystems known in the art.

Additional features and advantages will be set forth in part in thedescription that follows, and in part will be obvious from thedescription, or may be learned by practice of the embodiments disclosedherein. It is to be understood that both the foregoing brief summary andthe following detailed description are exemplary and explanatory onlyand are not restrictive of the embodiments disclosed herein or asclaimed.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 schematically illustrates a self-cleaning or self-disinfectingwater deliver system in which CSA molecules are introduced into a waterdelivery line that delivers water to a water storage vessel.

FIG. 2 schematically illustrates a self-cleaning water orself-disinfecting water deliver system in which CSA molecules areintroduced into a water storage vessel or well in fluid communicationwith a plurality of water delivery lines.

FIG. 3 schematically illustrates a CSA-releasing insert comprised of aninsert substrate and CSA molecules impregnated within the insertsubstrate.

FIG. 4 schematically illustrates a CSA-releasing insert comprised of aninsert substrate and a CSA-eluting composition coated on a surface ofthe insert substrate.

DETAILED DESCRIPTION I. Introduction

Disclosed herein are methods, systems, and inserts for cleaning ordisinfecting water delivery systems using cationic steroidalantimicrobial (CSA) molecules. Methods, systems, and inserts disclosedherein may beneficially clean or disinfect water delivery systems thatprovides drinking water to animals, such as agricultural animals, orhumans. CSA molecules can be added to a water deliver line used todeliver water. CSA molecules can be added to a water storage vessel orwell in communication with one or more water delivery lines. CSAmolecules can be used to clean water delivery lines or vessels used toprovide drinking water to animals, such as animals in a confined animalfeed operation. CSA molecules can be used to clean or disinfect aculinary water system that delivers culinary water to one or morelocations, such as homes or businesses. CSA molecules can usedformulated to kill microbes and/or break up biofilms within waterdelivery lines or water storage vessels and/or form complexes with metalions or metal compounds in water passing through water lines and/orcontained in water storage vessels.

II. CSA Molecules and Compositions

Cationic steroidal anti-microbial (CSA) molecules, sometimes referred toas CSA compounds or ceragenin compounds, can include syntheticallyproduced, small molecule chemical compounds that include a sterolbackbone having various charged groups (e.g., amine and cationic groups)attached to the backbone. The sterol backbone can be used to orientamine or guanidine groups on a face or plane of the sterol backbone.CSAs are cationic and amphiphilic, based upon the functional groupsattached to the backbone. They are facially amphiphilic with ahydrophobic face and a polycationic face.

Without wishing to be bound to theory, the CSA molecules describedherein act as anti-microbial agents (e.g., anti-bacterial, anti-fungal,and anti-viral). It is believed, for example, that anti-microbial CSAmolecules may act as an anti-microbial by binding to the cellularmembrane of bacteria and other microbes and modifying the cell membrane,e.g., such as by forming a pore that allows the leakage of ions andcytoplasmic materials critical to the microbe's survival, and leading tothe death of the affected microbe. In addition, anti-microbial CSAmolecules may also act to sensitize bacteria to other antibiotics. Forexample, at concentrations of anti-microbial CSA molecules below thecorresponding minimum bacteriostatic concentration (MIC), the CSAcompound may cause bacteria to become more susceptible to otherantibiotics by disrupting the cell membrane, such as by increasingmembrane permeability. It is postulated that charged cationic groups maybe responsible for disrupting the bacterial cellular membrane andimparting anti-microbial properties. CSA molecules may have similarmembrane- or outer coating-disrupting effects on fungi and viruses.

CSA molecules can also form complexes with metal ions or other dissolvedspecies contained within water, which can improve taste and/or reduceharmful effects of certains metals or other contaminates within water.

A. DEFINITIONS

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which these embodiments belong. The terminology used in thedescription herein is for describing particular embodiments only and isnot intended to be limiting of the embodiments. As used in thespecification and the appended claims, the singular forms “a,” “an,” and“the” are intended to include the plural forms as well, unless thecontext clearly indicates otherwise. All publications, patentapplications, patents, and other references mentioned herein areincorporated by reference in their entirety.

Terms and phrases used in this application, and variations thereof,especially in the appended claims, unless otherwise expressly stated,should be construed as open ended as opposed to limiting. As examples ofthe foregoing, the term “including” should be read to mean “including,without limitation,” “including but not limited to,” or the like; theterm “comprising” as used herein is synonymous with “including,”“containing,” or “characterized by,” and is inclusive or open-ended anddoes not exclude additional, unrecited elements or method steps; theterm “having” should be interpreted as “having at least”; the term“includes” should be interpreted as “includes but is not limited to”;the term “example” is used to provide exemplary instances of the item indiscussion, not an exhaustive or limiting list thereof; and use of termslike “preferably,” “preferred,” “desired,” or “desirable,” and words ofsimilar meaning should not be understood as implying that certainfeatures are critical, essential, or even important to the structure orfunction of the invention, but instead as merely intended to highlightalternative or additional features that may or may not be utilized in aparticular embodiment. In addition, the term “comprising” is to beinterpreted synonymously with the phrases “having at least” or“including at least”. When used in the context of a process, the term“comprising” means that the process includes at least the recited steps,but may include additional steps. When used in the context of acompound, composition or device, the term “comprising” means that thecompound, composition or device includes at least the recited featuresor components, but may also include additional features or components.Likewise, a group of items linked with the conjunction “and” should notbe read as requiring that each and every one of those items be presentin the grouping, but rather should be read as “and/or” unless expresslystated otherwise. Similarly, a group of items linked with theconjunction “or” should not be read as requiring mutual exclusivityamong that group, but rather should be read as “and/or” unless expresslystated otherwise.

It is understood that, in any compound described herein having one ormore chiral centers, if an absolute stereochemistry is not expresslyindicated, then each center may independently be of R-configuration orS-configuration or a mixture thereof. Thus, the compounds providedherein may be enantiomerically pure, enantiomerically enriched, racemicmixture, diastereomerically pure, diastereomerically enriched, or astereoisomeric mixture. In addition it is understood that, in anycompound described herein having one or more double bond(s) generatinggeometrical isomers that can be defined as E or Z, each double bond mayindependently be E or Z a mixture thereof.

Likewise, it is understood that, in any compound described, alltautomeric forms are also intended to be included.

It is to be understood that where compounds disclosed herein haveunfilled valencies, then the valencies are to be filled with hydrogensor isotopes thereof, e.g., hydrogen-1 (protium) and hydrogen-2(deuterium).

It is understood that the compounds described herein can be labeledisotopically. Substitution with isotopes such as deuterium may affordcertain therapeutic advantages resulting from greater metabolicstability, such as, for example, increased in vivo half-life or reduceddosage requirements. Each chemical element as represented in a compoundstructure may include any isotope of said element. For example, in acompound structure a hydrogen atom may be explicitly disclosed orunderstood to be present in the compound. At any position of thecompound that a hydrogen atom may be present, the hydrogen atom can beany isotope of hydrogen, including but not limited to hydrogen-1(protium) and hydrogen-2 (deuterium). Thus, reference herein to acompound encompasses all potential isotopic forms unless the contextclearly dictates otherwise.

It is understood that the methods and combinations described hereininclude crystalline forms (also known as polymorphs, which include thedifferent crystal packing arrangements of the same elemental compositionof a compound), amorphous phases, salts, solvates, and hydrates. In someembodiments, the compounds described herein exist in solvated forms withpharmaceutically acceptable solvents such as water, ethanol, or thelike. In other embodiments, the compounds described herein exist inunsolvated form. Solvates contain either stoichiometric ornon-stoichiometric amounts of a solvent, and may be formed during theprocess of crystallization with pharmaceutically acceptable solventssuch as water, ethanol, or the like. Hydrates are formed when thesolvent is water, or alcoholates are formed when the solvent is alcohol.In addition, the compounds provided herein can exist in unsolvated aswell as solvated forms. In general, the solvated forms are consideredequivalent to the unsolvated forms for the purposes of the compounds andmethods provided herein.

Unless otherwise indicated, all numbers expressing quantities ofingredients, reaction conditions, and so forth used in the specificationand claims are to be understood as being modified in all instances bythe term “about.” Accordingly, unless indicated to the contrary, thenumerical parameters set forth in the specification and attached claimsare approximations that may vary depending upon the desired propertiessought to be obtained by the present embodiments. At the very least, andnot as an attempt to limit the application of the doctrine ofequivalents to the scope of the claims, each numerical parameter shouldbe construed in light of the number of significant digits and ordinaryrounding approaches.

Notwithstanding that the numerical ranges and parameters setting forththe broad scope of the embodiments are approximations, the numericalvalues set forth in the specific examples are reported as precisely aspossible. Any numerical value, however, inherently contains certainerrors necessarily resulting from the standard deviation found in theirrespective testing measurements. Every numerical range given throughoutthis specification and claims will include every narrower numericalrange that falls within such broader numerical range, as if suchnarrower numerical ranges were all expressly written herein. Where arange of values is provided, it is understood that the upper and lowerlimit, and each intervening value between the upper and lower limit ofthe range is encompassed within the embodiments.

As used herein, any “R” group(s) such as, without limitation, R₁, R₂,R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₁₄, R₁₅, R₁₆, R₁₇, andR₁₈ represent substituents that can be attached to the indicated atom.Unless otherwise specified, an R group may be substituted orunsubstituted.

The term “ring” as used herein can be heterocyclic or carbocyclic. Theterm “saturated” used herein refers to a fused ring having each atom inthe fused ring either hydrogenated or substituted such that the valencyof each atom is filled. The term “unsaturated” used herein refers to afused ring where the valency of each atom of the fused ring may not befilled with hydrogen or other substituents. For example, adjacent carbonatoms in the fused ring can be doubly bound to each other. Unsaturationcan also include deleting at least one of the following pairs andcompleting the valence of the ring carbon atoms at these deletedpositions with a double bond; such as R₅ and R₉; R₈ and R₁₀; and R₁₃ andR₁₄.

Whenever a group is described as being “substituted” that group may besubstituted with one, two, three or more of the indicated substituents,which may be the same or different, each replacing a hydrogen atom. Ifno substituents are indicated, it is meant that the indicated“substituted” group may be substituted with one or more group(s)individually and independently selected from alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, cycloalkynyl, acylalkyl, alkoxyalkyl,aminoalkyl, amino acid, aryl, heteroaryl, heteroalicyclyl, aralkyl,heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, protected hydroxyl,alkoxy, aryloxy, acyl, mercapto, alkylthio, arylthio, cyano, halogen(e.g., F, Cl, Br, and I), thiocarbonyl, O-carbamyl, N-carbamyl,O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido,N-sulfonamido, C-carboxy, protected C-carboxy, O-carboxy, isocyanato,thiocyanato, isothiocyanato, nitro, oxo, silyl, sulfenyl, sulfinyl,sulfonyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl,trihalomethanesulfonamido, an amino, a mono-substituted amino group anda di-substituted amino group, R^(a)O(CH₂)_(m)O—, R^(b)(CH₂)_(n)O—,R^(c)C(O)O(CH₂)_(p)O—, and protected derivatives thereof. Thesubstituent may be attached to the group at more than one attachmentpoint. For example, an aryl group may be substituted with a heteroarylgroup at two attachment points to form a fused multicyclic aromatic ringsystem. Biphenyl and naphthalene are two examples of an aryl group thatis substituted with a second aryl group.

As used herein, “C_(a)” or “C_(a) to C_(b)” in which “a” and “b” areintegers refer to the number of carbon atoms in an alkyl, alkenyl oralkynyl group, or the number of carbon atoms in the ring of acycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl orheteroalicyclyl group. That is, the alkyl, alkenyl, alkynyl, ring of thecycloalkyl, ring of the cycloalkenyl, ring of the cycloalkynyl, ring ofthe aryl, ring of the heteroaryl or ring of the heteroalicyclyl cancontain from “a” to “b”, inclusive, carbon atoms. Thus, for example, a“C₁ to C₄ alkyl” group refers to all alkyl groups having from 1 to 4carbons, that is, CH₃—, CH₃CH₂—, CH₃CH₂CH₂—, (CH₃)₂CH—, CH₃CH₂CH₂CH₂—,CH₃CH₂CH(CH₃)— and (CH₃)₃C—. If no “a” and “b” are designated withregard to an alkyl, alkenyl, alkynyl, cycloalkyl cycloalkenyl,cycloalkynyl, aryl, heteroaryl or heteroalicyclyl group, the broadestrange described in these definitions is to be assumed.

As used herein, “alkyl” refers to a straight or branched hydrocarbonchain that comprises a fully saturated (no double or triple bonds)hydrocarbon group. The alkyl group may have 1 to 25 carbon atoms(whenever it appears herein, a numerical range such as “1 to 25” refersto each integer in the given range; e.g., “1 to 25 carbon atoms” meansthat the alkyl group may consist of 1 carbon atom, 2 carbon atoms, 3carbon atoms, etc., up to and including 25 carbon atoms, although thepresent definition also covers the occurrence of the term “alkyl” whereno numerical range is designated). The alkyl group may also be a mediumsize alkyl having 1 to 15 carbon atoms. The alkyl group could also be alower alkyl having 1 to 6 carbon atoms. The alkyl group of the compoundsmay be designated as “C₄” or “C₁-C₄ alkyl” or similar designations. Byway of example only, “C₁-C₄ alkyl” indicates that there are one to fourcarbon atoms in the alkyl chain, i.e., the alkyl chain is selected frommethyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, andt-butyl. Typical alkyl groups include, but are in no way limited to,methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl,pentyl and hexyl. The alkyl group may be substituted or unsubstituted.

As used herein, “alkenyl” refers to an alkyl group that contains in thestraight or branched hydrocarbon chain one or more double bonds. Thealkenyl group may have 2 to 25 carbon atoms (whenever it appears herein,a numerical range such as “2 to 25” refers to each integer in the givenrange; e.g., “2 to 25 carbon atoms” means that the alkenyl group mayconsist of 2 carbon atom, 3 carbon atoms, 4 carbon atoms, etc., up toand including 25 carbon atoms, although the present definition alsocovers the occurrence of the term “alkenyl” where no numerical range isdesignated). The alkenyl group may also be a medium size alkenyl having2 to 15 carbon atoms. The alkenyl group could also be a lower alkenylhaving 1 to 6 carbon atoms. The alkenyl group of the compounds may bedesignated as “C₄” or “C₂-C₄ alkenyl” or similar designations. Analkenyl group may be unsubstituted or substituted.

As used herein, “alkynyl” refers to an alkyl group that contains in thestraight or branched hydrocarbon chain one or more triple bonds. Thealkynyl group may have 2 to 25 carbon atoms (whenever it appears herein,a numerical range such as “2 to 25” refers to each integer in the givenrange; e.g., “2 to 25 carbon atoms” means that the alkynyl group mayconsist of 2 carbon atom, 3 carbon atoms, 4 carbon atoms, etc., up toand including 25 carbon atoms, although the present definition alsocovers the occurrence of the term “alkynyl” where no numerical range isdesignated). The alkynyl group may also be a medium size alkynyl having2 to 15 carbon atoms. The alkynyl group could also be a lower alkynylhaving 2 to 6 carbon atoms. The alkynyl group of the compounds may bedesignated as “C₄” or “C₂-C₄ alkynyl” or similar designations. Analkynyl group may be unsubstituted or substituted.

As used herein, “aryl” refers to a carbocyclic (all carbon) monocyclicor multicyclic aromatic ring system (including fused ring systems wheretwo carbocyclic rings share a chemical bond) that has a fullydelocalized pi-electron system throughout all the rings. The number ofcarbon atoms in an aryl group can vary. For example, the aryl group canbe a C₆-C₁₄ aryl group, a C₆-C₁₀ aryl group, or a C₆ aryl group(although the definition of C₆-C₁₀ aryl covers the occurrence of “aryl”when no numerical range is designated). Examples of aryl groups include,but are not limited to, benzene, naphthalene and azulene. An aryl groupmay be substituted or unsubstituted.

As used herein, “aralkyl” and “aryl(alkyl)” refer to an aryl groupconnected, as a substituent, via a lower alkylene group. The aralkylgroup may have 6 to 20 carbon atoms (whenever it appears herein, anumerical range such as “6 to 20” refers to each integer in the givenrange; e.g., “6 to 20 carbon atoms” means that the aralkyl group mayconsist of 6 carbon atom, 7 carbon atoms, 8 carbon atoms, etc., up toand including 20 carbon atoms, although the present definition alsocovers the occurrence of the term “aralkyl” where no numerical range isdesignated). The lower alkylene and aryl group of an aralkyl may besubstituted or unsubstituted. Examples include but are not limited tobenzyl, 2-phenylalkyl, 3-phenylalkyl, and naphthylalkyl.

“Lower alkylene groups” refer to a C₁-C₂₅ straight-chained alkyltethering groups, such as —CH₂— tethering groups, forming bonds toconnect molecular fragments via their terminal carbon atoms. Examplesinclude but are not limited to methylene (—CH₂—), ethylene (—CH₂CH₂—),propylene (—CH₂CH₂CH₂—), and butylene (—CH₂CH₂CH₂CH₂—). A lower alkylenegroup can be substituted by replacing one or more hydrogen of the loweralkylene group with a substituent(s) listed under the definition of“substituted.”

As used herein, “cycloalkyl” refers to a completely saturated (no doubleor triple bonds) mono- or multi-cyclic hydrocarbon ring system. Whencomposed of two or more rings, the rings may be joined together in afused fashion. Cycloalkyl groups can contain 3 to 10 atoms in thering(s) or 3 to 8 atoms in the ring(s). A cycloalkyl group may beunsubstituted or substituted. Typical cycloalkyl groups include, but arein no way limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl and cyclooctyl.

As used herein, “cycloalkenyl” refers to a mono- or multi-cyclichydrocarbon ring system that contains one or more double bonds in atleast one ring; although, if there is more than one, the double bondscannot form a fully delocalized pi-electron system throughout all therings (otherwise the group would be “aryl,” as defined herein). Whencomposed of two or more rings, the rings may be connected together in afused fashion. A cycloalkenyl group may be unsubstituted or substituted.

As used herein, “cycloalkynyl” refers to a mono- or multi-cyclichydrocarbon ring system that contains one or more triple bonds in atleast one ring. If there is more than one triple bond, the triple bondscannot form a fully delocalized pi-electron system throughout all therings. When composed of two or more rings, the rings may be joinedtogether in a fused fashion. A cycloalkynyl group may be unsubstitutedor substituted.

As used herein, “alkoxy” or “alkyloxy” refers to the formula —OR whereinR is an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl or acycloalkynyl as defined above. A non-limiting list of alkoxys includesmethoxy, ethoxy, n-propoxy, 1-methylethoxy (isopropoxy), n-butoxy,iso-butoxy, sec-butoxy and tert-butoxy. An alkoxy may be substituted orunsubstituted.

As used herein, “acyl” refers to a hydrogen, alkyl, alkenyl, alkynyl,aryl, or heteroaryl connected, as substituents, via a carbonyl group.Examples include formyl, acetyl, propanoyl, benzoyl, and acryl. An acylmay be substituted or unsubstituted.

As used herein, “alkoxyalkyl” or “alkyloxyalkyl” refers to an alkoxygroup connected, as a substituent, via a lower alkylene group. Examplesinclude alkyl-O-alkyl- and alkoxy-alkyl- with the terms alkyl and alkoxydefined herein.

As used herein, “hydroxyalkyl” refers to an alkyl group in which one ormore of the hydrogen atoms are replaced by a hydroxy group. Exemplaryhydroxyalkyl groups include but are not limited to, 2-hydroxyethyl,3-hydroxypropyl, 2-hydroxypropyl, and 2,2-dihydroxyethyl. A hydroxyalkylmay be substituted or unsubstituted.

As used herein, “haloalkyl” refers to an alkyl group in which one ormore of the hydrogen atoms are replaced by a halogen (e.g.,mono-haloalkyl, di-haloalkyl and tri-haloalkyl). Such groups include butare not limited to, chloromethyl, fluoromethyl, difluoromethyl,trifluoromethyl and 1-chloro-2-fluoromethyl, 2-fluoroisobutyl. Ahaloalkyl may be substituted or unsubstituted.

The term “amino” as used herein refers to a —NH₂ group.

As used herein, the term “hydroxy” refers to a —OH group.

A “cyano” group refers to a “—CN” group.

A “carbonyl” or an “oxo” group refers to a C═O group.

The term “azido” as used herein refers to a —N₃ group.

As used herein, “aminoalkyl” refers to an amino group connected, as asubstituent, via a lower alkylene group. Examples include H₂N-alkyl-with the term alkyl defined herein.

As used herein, “alkylcarboxyalkyl” refers to an alkyl group connected,as a substituent, to a carboxy group that is connected, as asubstituent, to an alkyl group. Examples include alkyl-C(═O)O-alkyl- andalkyl-O—C(═O)-alkyl- with the term alkyl as defined herein.

As used herein, “C-carboxyalkyl” refers to a carboxy group connected, asa substituent, to an alkyl group. Examples include HO—(C═O)-alkyl, withthe term alkyl as defined herein.

As used herein, “alkylaminoalkyl” refers to an alkyl group connected, asa substituent, to an amino group that is connected, as a substituent, toan alkyl group. Examples include alkyl-NH-alkyl-, with the term alkyl asdefined herein.

As used herein, “dialkylaminoalkyl” or “di(alkyl)aminoalkyl” refers totwo alkyl groups connected, each as a substituent, to an amino groupthat is connected, as a substituent, to an alkyl group. Examples include

with the term alkyl as defined herein.

As used herein, “alkylaminoalkylamino” refers to an alkyl groupconnected, as a substituent, to an amino group that is connected, as asubstituent, to an alkyl group that is connected, as a substituent, toan amino group. Examples include alkyl-NH-alkyl-NH—, with the term alkylas defined herein.

As used herein, “alkylaminoalkylaminoalkylamino” refers to an alkylgroup connected, as a substituent, to an amino group that is connected,as a substituent, to an alkyl group that is connected, as a substituent,to an amino group that is connected, as a substituent, to an alkylgroup. Examples include alkyl-NH-alkyl-NH-alkyl-, with the term alkyl asdefined herein.

As used herein, “arylaminoalkyl” refers to an aryl group connected, as asubstituent, to an amino group that is connected, as a substituent, toan alkyl group. Examples include aryl-NH-alkyl-, with the terms aryl andalkyl as defined herein.

As used herein, “aminoalkyloxy” refers to an amino group connected, as asubstituent, to an alkyloxy group. Examples include H₂N-alkyl-O— andH₂N-alkoxy- with the terms alkyl and alkoxy as defined herein.

As used herein, “aminoalkyloxyalkyl” refers to an amino group connected,as a substituent, to an alkyloxy group connected, as a substituent, toan alkyl group. Examples include H₂N-alkyl-O-alkyl- andH₂N-alkoxy-alkyl- with the terms alkyl and alkoxy as defined herein.

As used herein, “aminoalkylcarboxy” refers to an amino group connected,as a substituent, to an alkyl group connected, as a substituent, to acarboxy group. Examples include H₂N-alkyl-C(═O)O— and H₂N-alkyl-O—C(═O)—with the term alkyl as defined herein.

As used herein, “aminoalkylaminocarbonyl” refers to an amino groupconnected, as a substituent, to an alkyl group connected, as asubstituent, to an amino group connected, as a substituent, to acarbonyl group. Examples include H₂N-alkyl-NH—C(═O)— with the term alkylas defined herein.

As used herein, “aminoalkylcarboxamido” refers to an amino groupconnected, as a substituent, to an alkyl group connected, as asubstituent, to a carbonyl group connected, as a substituent to an aminogroup. Examples include H₂N-alkyl-C(═O)—NH— with the term alkyl asdefined herein.

As used herein, “azidoalkyloxy” refers to an azido group connected as asubstituent, to an alkyloxy group. Examples include N₃-alkyl-O— andN₃-alkoxy- with the terms alkyl and alkoxy as defined herein.

As used herein, “cyanoalkyloxy” refers to a cyano group connected as asubstituent, to an alkyloxy group. Examples include NC-alkyl-O— andNC-alkoxy- with the terms alkyl and alkoxy as defined herein.

As used herein, “guanidinoalkyloxy” refers to a guanidinyl groupconnected, as a substituent, to an alkyloxy group. Examples include

with the terms “alkyl” and “alkoxy” as defined herein.

As used herein, “guanidinoalkylcarboxy” refers to a guanidinyl groupconnected, as a substituent, to an alkyl group connected, as asubstituent, to a carboxy group. Examples include

with the term “alkyl” as defined herein.

As used herein, “quaternaryammoniumalkylcarboxy” refers to a quaternizedamino group connected, as a substituent, to an alkyl group connected, asa substituent, to a carboxy group. Examples include

with the term “alkyl” as defined herein.

The term “halogen atom” or “halogen” as used herein, means any one ofthe radio-stable atoms of column 7 of the Periodic Table of theElements, such as, fluorine, chlorine, bromine and iodine.

Where the numbers of substituents is not specified (e.g. haloalkyl),there may be one or more substituents present. For example “haloalkyl”may include one or more of the same or different halogens.

As used herein, the term “amino acid” refers to any amino acid (bothstandard and non-standard amino acids), including, but not limited to,α-amino acids, β-amino acids, γ-amino acids and δ-amino acids. Examplesof suitable amino acids include, but are not limited to, alanine,asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline,serine, tyrosine, arginine, histidine, isoleucine, leucine, lysine,methionine, phenylalanine, threonine, tryptophan and valine. Additionalexamples of suitable amino acids include, but are not limited to,ornithine, hypusine, 2-aminoisobutyric acid, dehydroalanine,gamma-aminobutyric acid, citrulline, beta-alanine, alpha-ethyl-glycine,alpha-propyl-glycine and norleucine.

A linking group is a divalent moiety used to link one steroid to anothersteroid. In some embodiments, the linking group is used to link a firstCSA with a second CSA (which may be the same or different). An exampleof a linking group is (C₁-C₁₀) alkyloxy-(C₁-C₁₀) alkyl.

The terms “P.G.” or “protecting group” or “protecting groups” as usedherein refer to any atom or group of atoms that is added to a moleculein order to prevent existing groups in the molecule from undergoingunwanted chemical reactions. Examples of protecting group moieties aredescribed in T. W. Greene and P. G. M. Wuts, Protective Groups inOrganic Synthesis, 3. Ed. John Wiley & Sons, 1999, and in J. F. W.McOmie, Protective Groups in Organic Chemistry Plenum Press, 1973, bothof which are hereby incorporated by reference for the limited purpose ofdisclosing suitable protecting groups. The protecting group moiety maybe chosen in such a way, that they are stable to certain reactionconditions and readily removed at a convenient stage using methodologyknown from the art. A non-limiting list of protecting groups includebenzyl; substituted benzyl; alkylcarbonyls and alkoxycarbonyls (e.g.,t-butoxycarbonyl (BOC), acetyl, or isobutyryl); arylalkylcarbonyls andarylalkoxycarbonyls (e.g., benzyloxycarbonyl); substituted methyl ether(e.g. methoxymethyl ether); substituted ethyl ether; a substitutedbenzyl ether; tetrahydropyranyl ether; silyls (e.g., trimethylsilyl,triethylsilyl, triisopropylsilyl, t-butyldimethylsilyl,tri-iso-propylsilyloxymethyl, [2-(trimethylsilyl)ethoxy]methyl ort-butyldiphenylsilyl); esters (e.g. benzoate ester); carbonates (e.g.methoxymethyl-carbonate); sulfonates (e.g. tosylate or mesylate);acyclic ketal (e.g. dimethyl acetal); cyclic ketals (e.g., 1,3-dioxane,1,3-dioxolanes, and those described herein); acyclic acetal; cyclicacetal (e.g., those described herein); acyclic hemiacetal; cyclichemiacetal; cyclic dithioketals (e.g., 1,3-dithiane or 1,3-dithiolane);orthoesters (e.g., those described herein) and triarylmethyl groups(e.g., trityl; monomethoxytrityl (MMTr); 4,4′-dimethoxytrityl (DMTr);4,4′,4″-trimethoxytrityl (TMTr); and those described herein).Amino-protecting groups are known to those skilled in the art. Ingeneral, the species of protecting group is not critical, provided thatit is stable to the conditions of any subsequent reaction(s) on otherpositions of the compound and can be removed at the appropriate pointwithout adversely affecting the remainder of the molecule. In addition,a protecting group may be substituted for another after substantivesynthetic transformations are complete. Clearly, where a CSA compounddiffers from a compound disclosed herein only in that one or moreprotecting groups of the disclosed compound has been substituted with adifferent protecting group, that compound is within the disclosure

Anti-microbial CSA compounds may also include a tether or “tail moiety”attached to the sterol backbone. The tail moiety may have variable chainlength or size and may be one of charged, uncharged, polar, non-polar,hydrophobic, amphipathic, and the like. In various embodiments, a tailmoiety may be attached at R₁₇. A tail moiety may include the heteroatom(O or N) covalently coupled to the sterol backbone. The tail moiety may,for example, be configured to alter the hydrophobicity/hydrophilicity ofthe CSA compound. CSA compounds of the present disclosure havingdifferent degrees of hydrophobicity/hydrophilicity may, for example,have different rates of uptake into different target microbes. Likewise,altering the hydrophobicity and/or hydrophilicity of the CSA compoundsdescribed herein can affect the retention of the CSA compounds incertain media.

B. CSA COMPOUNDS OR MOLECULES

CSA compounds (also referred to herein as “CSA molecules”) useful inaccordance with this disclosure are described herein, both genericallyand with particularity, and in U.S. Pat. Nos. 6,350,738, 6,486,148,6,767,904, 7,598,234, 7,754,705, U.S. Application Ser. Nos. 61/786,301,13/288,892, 61/642,431, 13/554,930, 61/572,714, 13/594,608, 61/576,903,13/594,612, 13/288,902, 61/605,639, 13/783,131, 61/605,642, 13/783,007,61/132,361, 13/000,010, 61/534,185, 13/615,244, 61/534,194, 13/615,324,61/534,205, 61/637,402, 13/841,549, 61/715,277, PCT/US13/37615,61/749,800, 61/794,721, and 61/814,816, which are incorporated herein byreference. Additional molecules or compounds are generally andspecifically described in relation to the methods discussed herein. Theskilled artisan will recognize the compounds within the generic formulaeset forth herein and understand their preparation in view of thereferences cited herein and the Examples.

In some embodiments, the CSA is a compound of Formula (I) or a saltthereof:

wherein:

rings A, B, C, and D are independently saturated, or are fully orpartially unsaturated, provided that at least two of rings A, B, C, andD are saturated;

m, n, p, and q are independently 0 or 1;

R₁ through R₄, R₆, R₇, R₁₁, R₁₂, R₁₅, R₁₆, and R₁₈ are independentlyselected from the group consisting of hydrogen, hydroxyl, a substitutedor unsubstituted alkyl, a substituted or unsubstituted hydroxyalkyl, asubstituted or unsubstituted alkyloxyalkyl, a substituted orunsubstituted alkylcarboxyalkyl, a substituted or unsubstitutedalkylaminoalkyl, a substituted or unsubstituted alkylaminoalkylamino, asubstituted or unsubstituted alkylaminoalkylaminoalkylamino, asubstituted or unsubstituted aminoalkyl, a substituted or unsubstitutedaryl, a substituted or unsubstituted arylaminoalkyl, a substituted orunsubstituted haloalkyl, a substituted or unsubstituted alkenyl, asubstituted or unsubstituted alkynyl, oxo, a linking group attached to asecond steroid, a substituted or unsubstituted aminoalkyloxy, asubstituted or unsubstituted aminoalkyloxyalkyl, a substituted orunsubstituted aminoalkylcarboxy, a substituted or unsubstitutedaminoalkylaminocarbonyl, a substituted or unsubstitutedaminoalkylcarboxamido, a substituted or unsubstituteddi(alkyl)aminoalkyl, H₂N—HC(Q₅)-C(O)—O—, H₂N—HC(Q₅)-C(O)—N(H)—, asubstituted or unsubstituted azidoalkyloxy, a substituted orunsubstituted cyanoalkyloxy, P.G.-HN—HC(Q₅)-C(O)—O—, a substituted orunsubstituted guanidinoalkyloxy, a substituted or unsubstitutedquaternaryammoniumalkylcarboxy, and a substituted or unsubstitutedguanidinoalkyl carboxy, where Q₅ is a side chain of any amino acid(including a side chain of glycine, i.e., H), and P.G. is an aminoprotecting group; and

R₅, R₈, R₉, R₁₀, R₁₃, R₁₄ and R₁₇ are independently deleted when one ofrings A, B, C, or D is unsaturated so as to complete the valency of thecarbon atom at that site, or R₅, R₈, R₉, R₁₀, R₁₃, and R₁₄ areindependently selected from the group consisting of hydrogen, hydroxyl,a substituted or unsubstituted alkyl, a substituted or unsubstitutedhydroxyalkyl, a substituted or unsubstituted alkyloxyalkyl, asubstituted or unsubstituted aminoalkyl, a substituted or unsubstitutedaryl, a substituted or unsubstituted haloalkyl, a substituted orunsubstituted alkenyl, a substituted or unsubstituted alkynyl, oxo, alinking group attached to a second steroid, a substituted orunsubstituted aminoalkyloxy, a substituted or unsubstitutedaminoalkylcarboxy, a substituted or unsubstitutedaminoalkylaminocarbonyl, a substituted or unsubstituteddi(alkyl)aminoalkyl, H₂N—HC(Q₅)-C(O)—O—, H₂N—HC(Q₅)-C(O)—N(H)—,azidoalkyloxy, cyanoalkyloxy, P.G.-HN—HC(Q₅)-C(O)—O—, guanidinoalkyloxy,and guanidinoalkylcarboxy, where Q₅ is a side chain of any amino acid,P.G. is an amino protecting group,

provided that at least two or three of R₁₋₄, R₆, R₇, R₁₁, R₁₂, R₁₅, R₁₆,R₁₇, and R₁₈ are independently selected from the group consisting of asubstituted or unsubstituted aminoalkyl, a substituted or unsubstitutedaminoalkyloxy, a substituted or unsubstituted alkylcarboxyalkyl, asubstituted or unsubstituted alkylaminoalkylamino, a substituted orunsubstituted alkylaminoalkylaminoalkylamino, a substituted orunsubstituted aminoalkylcarboxy, a substituted or unsubstitutedarylaminoalkyl, a substituted or unsubstitutedaminoalkyloxyaminoalkylaminocarbonyl, a substituted or unsubstitutedaminoalkylaminocarbonyl, a substituted or unsubstitutedaminoalkylcarboxyamido, a quaternaryammoniumalkylcarboxy, a substitutedor unsubstituted di(alkyl)aminoalkyl, H₂N—HC(Q₅)-C(O)—O—,H₂N—HC(Q₅)-C(O)—N(H)—, azidoalkyloxy, cyanoalkyloxy,P.G.-HN—HC(Q₅)-C(O)—O—, a substituted or unsubstitutedguanidine-alkyloxy, and a substituted or unsubstitutedguanidinoalkylcarboxy.

In some embodiments, R₁ through R₄, R₆, R₇, R₁₁, R₁₂, R₁₅, R₁₆, and R₁₈are independently selected from the group consisting of hydrogen,hydroxyl, a substituted or unsubstituted (C₁-C₂₂) alkyl, a substitutedor unsubstituted (C₁-C₂₂) hydroxyalkyl, a substituted or unsubstituted(C₁-C₂₂) alkyloxy-(C₁-C₂₂) alkyl, a substituted or unsubstituted(C₁-C₂₂) alkylcarboxy-(C₁-C₂₂) alkyl, a substituted or unsubstituted(C₁-C₂₂) alkylamino-(C₁-C₂₂) alkyl, a substituted or unsubstituted(C₁-C₂₂) alkylamino-(C₁-C₂₂) alkylamino, a substituted or unsubstituted(C₁-C₂₂) alkylamino-(C₁-C₂₂) alkylamino-(C₁-C₂₂) alkylamino, asubstituted or unsubstituted (C₁-C₂₂) aminoalkyl, a substituted orunsubstituted aryl, a substituted or unsubstituted arylamino-(C₁-C₂₂)alkyl, a substituted or unsubstituted (C₁-C₂₂) haloalkyl, a substitutedor unsubstituted C₂-C₆ alkenyl, a substituted or unsubstituted C₂-C₆alkynyl, oxo, a linking group attached to a second steroid, asubstituted or unsubstituted (C₁-C₂₂) aminoalkyloxy, a substituted orunsubstituted (C₁-C₂₂) aminoalkyloxy-(C₁-C₂₂) alkyl, a substituted orunsubstituted (C₁-C₂₂) aminoalkylcarboxy, a substituted or unsubstituted(C₁-C₂₂) aminoalkylaminocarbonyl, a substituted or unsubstituted(C₁-C₂₂) aminoalkylcarboxamido, a substituted or unsubstituted di(C₁-C₂₂alkyl)aminoalkyl, H₂N—HC(Q₅)-C(O)—O—, H₂N—HC(Q₅)-C(O)—N(H)—, asubstituted or unsubstituted (C₁-C₂₂) azidoalkyloxy, a substituted orunsubstituted (C₁-C₂₂) cyanoalkyloxy, P.G.-HN—HC(Q₅)-C(O)—O—, asubstituted or unsubstituted (C₁-C₂₂) guanidinoalkyloxy, a substitutedor unsubstituted (C₁-C₂₂) quaternaryammoniumalkylcarboxy, and asubstituted or unsubstituted (C₁-C₂₂) guanidinoalkyl carboxy, where Q₅is a side chain of any amino acid (including a side chain of glycine,i.e., H), and P.G. is an amino protecting group.

R₅, R₈, R₉, R₁₀, R₁₃, R₁₄ and R₁₇ are independently deleted when one ofrings A, B, C, or D is unsaturated so as to complete the valency of thecarbon atom at that site, or R₅, R₈, R₉, R₁₀, R₁₃, and R₁₄ areindependently selected from the group consisting of hydrogen, hydroxyl,a substituted or unsubstituted (C₁-C₂₂) alkyl, a substituted orunsubstituted (C₁-C₂₂) hydroxyalkyl, a substituted or unsubstituted(C₁-C₂₂) alkyloxy-(C₁-C₂₂) alkyl, a substituted or unsubstituted(C₁-C₂₂) aminoalkyl, a substituted or unsubstituted aryl, a substitutedor unsubstituted (C₁-C₂₂) haloalkyl, a substituted or unsubstituted(C₂-C₆) alkenyl, a substituted or unsubstituted (C₂-C₆) alkynyl, oxo, alinking group attached to a second steroid, a substituted orunsubstituted (C₁-C₂₂) aminoalkyloxy, a substituted or unsubstituted(C₁-C₂₂) aminoalkylcarboxy, a substituted or unsubstituted (C₁-C₂₂)aminoalkylaminocarbonyl, a substituted or unsubstituted di(C₁-C₂₂alkyl)aminoalkyl, H₂N—HC(Q₅)-C(O)—O—, H₂N—HC(Q₅)-C(O)—N(H)—, asubstituted or unsubstituted (C₁-C₂₂) azidoalkyloxy, a substituted orunsubstituted (C₁-C₂₂) cyanoalkyloxy, P.G.-HN—HC(Q₅)-C(O)—O—, asubstituted or unsubstituted (C₁-C₂₂) guanidinoalkyloxy, and (C₁-C₂₂)guanidinoalkylcarboxy, where Q₅ is a side chain of any amino acid, andP.G. is an amino protecting group; provided that at least two or threeof R₁₋₄, R₆, R₇, R₁₁, R₁₂, R₁₅, R₁₆, R₁₇, and R₁₈ are independentlyselected from the group consisting of a substituted or unsubstituted(C₁-C₂₂) aminoalkyl, a substituted or unsubstituted (C₁-C₂₂)aminoalkyloxy, a substituted or unsubstituted (C₁-C₂₂)alkylcarboxy-(C₁-C₂₂) alkyl, a substituted or unsubstituted (C₁-C₂₂)alkylamino-(C₁-C₂₂) alkylamino, a substituted or unsubstituted (C₁-C₂₂)alkylamino-(C₁-C₂₂) alkylamino (C₁-C₂₂) alkylamino, a substituted orunsubstituted (C₁-C₂₂) aminoalkylcarboxy, a substituted or unsubstitutedarylamino (C₁-C₂₂) alkyl, a substituted or unsubstituted (C₁-C₂₂)aminoalkyloxy (C₁-C₂₂) aminoalkylaminocarbonyl, a substituted orunsubstituted (C₁-C₂₂) aminoalkylaminocarbonyl, a substituted orunsubstituted (C₁-C₂₂) aminoalkylcarboxyamido, a substituted orunsubstituted (C₁-C₂₂) quaternary ammonium alkylcarboxy, a substitutedor unsubstituted di(C₁-C₂₂ alkyl)aminoalkyl, H₂N—HC(Q₅)-C(O)—O—,H₂N—HC(Q₅)-C(O)—N(H)—, a substituted or unsubstituted (C₁-C₂₂)azidoalkyloxy, a substituted or unsubstituted (C₁-C₂₂) cyanoalkyloxy,P.G.-HN—HC(Q₅)-C(O)—O—, a substituted or unsubstituted (C₁-C₂₂)guanidinoalkyloxy, and a substituted or unsubstituted (C₁-C₂₂)guanidinoalkylcarboxy.

In some embodiments, R₁ through R₄, R₆, R₇, R₁₁, R₁₂, R₁₅, R₁₆, and R₁₈are independently selected from the group consisting of hydrogen,hydroxyl, an unsubstituted (C₁-C₁₈) alkyl, unsubstituted (C₁-C₁₈)hydroxyalkyl, unsubstituted (C₁-C₁₈) alkyloxy-(C₁-C₁₈) alkyl,unsubstituted (C₁-C₁₈) alkylcarboxy-(C₁-C₁₈) alkyl, unsubstituted(C₁-C₁₈) alkylamino-(C₁-C₁₈)alkyl, unsubstituted (C₁-C₁₈)alkylamino-(C₁-C₁₈) alkylamino, (C₁-C₁₈) alkylamino-(C₁-C₁₈)alkylamino-(C₁-C₁₈) alkylamino, an unsubstituted (C₁-C₁₈) aminoalkyl, anunsubstituted aryl, an unsubstituted arylamino-(C₁-C₁₈) alkyl, oxo, anunsubstituted (C₁-C₁₈) aminoalkyloxy, an unsubstituted (C₁-C₁₈)aminoalkyloxy-(C₁-C₁₈) alkyl, an unsubstituted (C₁-C₁₈)aminoalkylcarboxy, an unsubstituted (C₁-C₁₈) aminoalkylaminocarbonyl, anunsubstituted(C₁-C₁₈) aminoalkylcarboxamido, an unsubstituted di(C₁-C₁₈alkyl)aminoalkyl, unsubstituted (C₁-C₁₈) guanidinoalkyloxy,unsubstituted (C₁-C₁₈) quaternary ammonium alkylcarboxy, andunsubstituted (C₁-C₁₈) guanidinoalkyl carboxy; R₅, R₈, R₉, R₁₀, R₁₃, R₁₄and R₁₇ are independently deleted when one of rings A, B, C, or D isunsaturated so as to complete the valency of the carbon atom at thatsite, or R₅, R₈, R₉, R₁₀, R₁₃, and R₁₄ are independently selected fromthe group consisting of hydrogen, hydroxyl, an unsubstituted (C₁-C₁₈)alkyl, unsubstituted (C₁-C₁₈) hydroxyalkyl, unsubstituted (C₁-C₁₈)alkyloxy-(C₁-C₁₈) alkyl, unsubstituted (C₁-C₁₈) alkylcarboxy-(C₁-C₁₈)alkyl, unsubstituted (C₁-C₁₈) alkylamino-(C₁-C₁₈)alkyl, (C₁-C₁₈)alkylamino-(C₁-C₁₈) alkylamino, unsubstituted (C₁-C₁₈)alkylamino-(C₁-C₁₈) alkylamino-(C₁-C₁₈) alkylamino, an unsubstituted(C₁-C₁₈) aminoalkyl, an unsubstituted aryl, an unsubstitutedarylamino-(C₁-C₁₈) alkyl, oxo, an unsubstituted (C₁-C₁₈) aminoalkyloxy,an unsubstituted (C₁-C₁₈) aminoalkyloxy-(C₁-C₁₈) alkyl, an unsubstituted(C₁-C₁₈) aminoalkylcarboxy, an unsubstituted (C₁-C₁₈)aminoalkylaminocarbonyl, an unsubstituted (C₁-C₁₈)aminoalkylcarboxamido, an unsubstituted di(C₁-C₁₈ alkyl)aminoalkyl,unsubstituted (C₁-C₁₈) guanidinoalkyloxy, unsubstituted (C₁-C₁₈)quaternaryammoniumalkylcarboxy, and unsubstituted (C₁-C₁₈)guanidinoalkyl carboxy; provided that at least two or three of R₁₋₄, R₆,R₇, R₁₁, R₁₂, R₁₅, R₁₆, R₁₇, and R₁₈ are independently selected from thegroup consisting of hydrogen, hydroxyl, an unsubstituted (C₁-C₁₈) alkyl,unsubstituted (C₁-C₁₈) hydroxyalkyl, unsubstituted (C₁-C₁₈)alkyloxy-(C₁-C₁₈) alkyl, unsubstituted (C₁-C₁₈) alkylcarboxy-(C₁-C₁₈)alkyl, unsubstituted (C₁-C₁₈) alkylamino-(C₁-C₁₈) alkyl, unsubstituted(C₁-C₁₈) alkylamino-(C₁-C₁₈) alkylamino, unsubstituted (C₁-C₁₈)alkylamino-(C₁-C₁₈) alkylamino-(C₁-C₁₈) alkylamino, an unsubstituted(C₁-C₁₈) aminoalkyl, an unsubstituted aryl, an unsubstitutedarylamino-(C₁-C₁₈) alkyl, oxo, an unsubstituted (C₁-C₁₈) aminoalkyloxy,an unsubstituted (C₁-C₁₈) aminoalkyloxy-(C₁-C₁₈) alkyl, an unsubstituted(C₁-C₁₈) aminoalkylcarboxy, an unsubstituted (C₁-C₁₈)aminoalkylaminocarbonyl, an unsubstituted (C₁-C₁₈)aminoalkylcarboxamido, an unsubstituted di(C₁-C₁₈ alkyl) amino alkyl,unsubstituted (C₁-C₁₈) guanidinoalkyloxy, unsubstituted (C₁-C₁₈)quaternaryammoniumalkylcarboxy, and unsubstituted (C₁-C₁₈)guanidinoalkyl carboxy.

In some embodiments, the CSA, or a salt thereof, is selected from thecompound of Formula (IA), which is a subgenus of Formula (I) in that R₁₅is omitted:

In some embodiments, rings A, B, C, and D are independently saturated.

In some embodiments, one or more of rings A, B, C, and D areheterocyclic.

In some embodiments, rings A, B, C, and D are non-heterocyclic.

In some embodiments, R₃, R₇, R₁₂, and R₁₈ are independently selectedfrom the group consisting of hydrogen, an unsubstituted (C₁-C₁₈) alkyl,unsubstituted (C₁-C₁₈) hydroxyalkyl, unsubstituted (C₁-C₁₈)alkyloxy-(C₁-C₁₈) alkyl, unsubstituted (C₁-C₁₈) alkylcarboxy-(C₁-C₁₈)alkyl, unsubstituted (C₁-C₁₈) alkylamino-(C₁-C₁₈)alkyl, unsubstituted(C₁-C₁₈) alkylamino-(C₁-C₁₈) alkylamino, unsubstituted (C₁-C₁₈)alkylamino-(C₁-C₁₈) alkylamino-(C₁-C₁₈) alkylamino, an unsubstituted(C₁-C₁₈) aminoalkyl, an unsubstituted arylamino-(C₁-C₁₈) alkyl, anunsubstituted (C₁-C₁₈) aminoalkyloxy, an unsubstituted (C₁-C₁₈)aminoalkyloxy-(C₁-C₁₈) alkyl, an unsubstituted (C₁-C₁₈)aminoalkylcarboxy, an unsubstituted (C₁-C₁₈) aminoalkylaminocarbonyl, anunsubstituted (C₁-C₁₈) aminoalkylcarboxamido, an unsubstituted di(C₁-C₁₈alkyl) amino alkyl, unsubstituted (C₁-C₁₈) guanidinoalkyloxy,unsubstituted (C₁-C₁₈) quaternary ammonium alkylcarboxy, andunsubstituted (C₁-C₁₈) guanidinoalkyl carboxy; and R₁, R₂, R₄, R₅, R₆,R₈, R₉, R₁₀, R₁₁, R₁₃, R₁₄, R₁₅, R₁₆, and R₁₇ are independently selectedfrom the group consisting of hydrogen and unsubstituted (C₁-C₆) alkyl.

In some embodiments, R₃, R₇, R₁₂, and R₁₈ are independently selectedfrom the group consisting of hydrogen, an unsubstituted (C₁-C₆) alkyl,unsubstituted (C₁-C₆) hydroxyalkyl, unsubstituted (C₁-C₁₆)alkyloxy-(C₁-C₅) alkyl, unsubstituted (C₁-C₁₆) alkylcarboxy-(C₁-C₅)alkyl, unsubstituted (C₁-C₁₆) alkylamino-(C₁-C₅)alkyl, unsubstituted(C₁-C₁₆) alkylamino-(C₁-C₅) alkylamino, unsubstituted (C₁-C₁₆)alkylamino-(C₁-C₁₆) alkylamino-(C₁-C₅) alkylamino, an unsubstituted(C₁-C₁₆) aminoalkyl, an unsubstituted arylamino-(C₁-C₅) alkyl, anunsubstituted (C₁-C₅) aminoalkyloxy, an unsubstituted (C₁-C₁₆)aminoalkyloxy-(C₁-C₅) alkyl, an unsubstituted (C₁-C₅) aminoalkylcarboxy,an unsubstituted (C₁-C₅) aminoalkylaminocarbonyl, an unsubstituted(C₁-C₅) aminoalkylcarboxamido, an unsubstituted di(C₁-C₅alkyl)amino-(C₁-C₅) alkyl, unsubstituted (C₁-C₅) guanidinoalkyloxy,unsubstituted (C₁-C₁₆) quaternaryammoniumalkylcarboxy, and unsubstituted(C₁-C₁₆) guanidinoalkylcarboxy.

In some embodiments, R₁, R₂, R₄, R₅, R₆, R₈, R₁₀, R₁₁, R₁₄, R₁₆, and R₁₇are each hydrogen; and R₉ and R₁₃ are each methyl.

In some embodiments, R₃, R₇, R₁₂, and R₁₈ are independently selectedfrom the group consisting of aminoalkyloxy; aminoalkylcarboxy;alkylaminoalkyl; alkoxycarbonylalkyl; alkylcarbonylalkyl;di(alkyl)aminoalkyl; alkylcarboxyalkyl; and hydroxyalkyl.

In some embodiments, R₃, R₇, and R₁₂ are independently selected from thegroup consisting of aminoalkyloxy and aminoalkylcarboxy; and R₁₈ isselected from the group consisting of alkylaminoalkyl;alkoxycarbonylalkyl; alkylcarbonyloxyalkyl; di(alkyl)aminoalkyl;alkylaminoalkyl; alkyoxycarbonylalkyl; alkylcarboxyalkyl; andhydroxyalkyl.

In some embodiments, R₃, R₇, and R₁₂ are the same. In some embodiments,R₃, R₇, and R₁₂ are aminoalkyloxy. In some embodiments, R₃, R₇, and R₁₂are aminoalkylcarboxy. In some embodiments, R₁₈ is alkylaminoalkyl. Insome embodiments, R₁₈ is alkoxycarbonylalkyl. In some embodiments, R₁₈is di(alkyl)aminoalkyl. In some embodiments, R₁₈ is alkylcarboxyalkyl.In some embodiments, R₁₈ is hydroxyalkyl.

In some embodiments, R₃, R₇, R₁₂, and R₁₈ are independently selectedfrom the group consisting of amino-C₃-alkyloxy; amino-C₃-alkyl-carboxy;C₈-alkylamino-C₅-alkyl; C₈-alkoxy-carbonyl-C₄-alkyl;C₈-alkyl-carbonyl-C₄-alkyl; di-(C₅-alkyl)amino-C₅-alkyl;C₁₃-alkylamino-C₅-alkyl; C₆-alkoxy-carbonyl-C₄-alkyl;C₆-alkyl-carboxy-C₄-alkyl; and C₁₆-alkylamino-C₅-alkyl.

In some embodiments, at least two, or at least three, of m, n, p, and qare 1. In some embodiments, m, n, and p are each 1 and q is 0.

In some embodiments, the CSA, or a salt thereof, is selected from thecompound of Formula (IB), which is a subgenus of Formula (IA):

In some embodiments, the CSA, or a salt thereof of the compound ofFormula (IB), is selected from the group consisting of:

and salts thereof.

C. SALTS

The compounds and compositions disclosed herein are optionally preparedas salts. The term “salt” as used herein is a broad term, and is to begiven its ordinary and customary meaning to a skilled artisan (and isnot to be limited to a special or customized meaning), and referswithout limitation to a salt of a compound. In some embodiments, thesalt is an acid addition salt of the compound. Salts can be obtained byreacting a compound with inorganic acids such as hydrohalic acid (e.g.,hydrochloric acid or hydrobromic acid), sulfuric acid, nitric acid, andphosphoric acid. Salts can also be obtained by reacting a compound withan organic acid such as aliphatic or aromatic carboxylic or sulfonicacids, for example formic acid, acetic acid, propionic acid, glycolicacid, pyruvic acid, malonic acid, maleic acid, fumaric acid,trifluoroacetic acid, benzoic acid, cinnamic acid, mandelic acid,succinic acid, lactic acid, malic acid, tartaric acid, citric acid,ascorbic acid, nicotinic acid, methanesulfonic acid, ethanesulfonicacid, p-toluenesulfonic acid, salicylic acid, stearic acid, muconicacid, butyric acid, phenylacetic acid, phenylbutyric acid, valproicacid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid,benzenesulfonic acid, 2-naphthalenesulfonic acid, or naphthalenesulfonicacid. Salts can also be obtained by reacting a compound with a base toform a salt such as an ammonium salt, an alkali metal salt, such as alithium, sodium or a potassium salt, an alkaline earth metal salt, suchas a calcium, magnesium or aluminum salt, a salt of organic bases suchas dicyclohexylamine, N-methyl-D-glucamine,tris(hydroxymethyl)methylamine, C₁-C₇ alkylamine, cyclohexylamine,dicyclohexylamine, triethanolamine, ethylenediamine, ethanolamine,diethanolamine, triethanolamine, tromethamine, and salts with aminoacids such as arginine and lysine; or a salt of an inorganic base, suchas aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodiumcarbonate, sodium hydroxide, or the like.

In some embodiments, the salt is a hydrochloride salt. In someembodiments, the salt is a mono-hydrochloride salt, a di-hydrochloridesalt, a tri-hydrochloride salt, or a tetra-hydrochloride salt.Additional examples of salts include sulfuric acid addition salts andsulfonic acid addition salts. 1,5-naphthalenedisulfonic acid is aparticularly useful sulfonic acid addition salt.

III. Methods for Cleaning or Disinfecting a Water Deliver System

According to some embodiments, a method for cleaning or disinfecting awater delivery system, such as a water delivery line comprises: (1)adding cationic steroidal antimicrobial (CSA) molecules to water to forman aqueous CSA composition; and (2) passing the aqueous CSA compositionthrough the water delivery line in order to clean or disinfect the waterdelivery line. For example, a method for cleaning or disinfecting awater delivery line that delivers drinking water to animals comprises:(1) adding cationic steroidal antimicrobial (CSA) molecules to the waterdelivery line to form an aqueous CSA composition; and (2) passing theaqueous CSA composition through the water delivery line in order toclean or disinfect the water line.

In some embodiments, a method for cleaning or disinfecting a waterdelivery system comprised of a water storage vessel or well and a waterdelivery line in fluid communication with the water storage vessel orwell comprises: (1) adding cationic steroidal antimicrobial (CSA)molecules to water to form an aqueous CSA composition; and (2) passingthe aqueous CSA composition through at least one of the water deliveryline or water storage vessel. The aqueous CSA composition can beperiodically passed through a water delivery line, followed byperiodically passing water without CSA molecules through the waterdelivery line.

The aqueous CSA compositions used to clean or disinfect a water deliverysystem can be prepared in any desired manner. In some embodiments, CSAmolecules are added directly to at least one of a water delivery line,well, or storage vessel. The CSA molecules can also be combined with aliquid or solid to form a CSA delivery composition, which can becontacted with water in order to provide CSA molecules to one or morecomponents of a water delivery system. CSA molecules can be mixed withwater to form a concentrated CSA composition that is introduced into atleast one of a water delivery line, well, or storage vessel to form anaqueous CSA composition. The CSA delivery composition can be aCSA-containing table, powder, CSA-eluting composition, or CSA-elutingdevice. The method may comprise placing a CSA-containing tablet, powder,or eluting device into a storage vessel upstream from the water deliveryline. A CSA-eluting insert can be positioned within or form part of awater delivery line or water storage vessel.

In some embodiments, a CSA-eluting composition is applied to an interiorsurface of a water delivery line and/or a water storage vessel. TheCSA-eluting composition releases CSA molecules into water over time,thereby providing at least a portion of the CSA molecules added to waterto form an aqueous CSA composition. The water storage vessel may bepositioned upstream from a water delivery line, wherein the CSA-elutingcomposition releases at least a portion of the CSA molecules added towater to form an aqueous CSA composition. The water storage vessel maybe positioned so as to receive water from a water delivery line (e.g.,can be an animal watering trough or vessel).

The aqueous CSA compositions used to clean or disinfect a water deliverysystem can have a concentration of CSA molecules that is able to killmicrobes and/or break up biofilms located within the water deliverysystem. The optimal concentration may depend on several factors, such asthe type of CSA molecules, the contact time of the aqueous CSAcompositions and interior surfaces within the water delivery system, theamount of microbes or biofilms within the water delivery system, and theintended use of the cleaned or disinfected water. Suitableconcentrations of CSA molecules in the aqueous CSA compositions can beat least 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1%,0.5%, or 1% by weight and/or less than 5%, 1%, 0.5%, 0.1%, 0.05%, or0.01% by weight and/or within a concentration range defined by the anyof the foregoing as lower and upper range endpoints. In someembodiments, the concentration may be at least 0.5 ppm, 1 ppm, 2 ppm, 5ppm, 10 ppm, 50 ppm, 100 ppm, 500 ppm, or 1000 ppm and/or less than 5000ppm, 1000 ppm, 500 ppm, 100 ppm, 50 ppm, or 10 ppm and/or within aconcentration range defined by the any of the foregoing as lower andupper range endpoints.

In some embodiments, the methods involve cleaning or disinfecting awater delivery line and/or water storage vessel which provides drinkingwater to animals, including but not limited to, at least one of cattle,horses, sheep, swine, or poultry (e.g., turkeys or chickens). Suchmethods are particularly advantageous in the case of confined animalfeed operations, where diseases can be more easily spread and/or whereinfections can occur rapidly when animals are given contaminated water.

In addition to helping prevent infections and/or spread of infectionsamong animals, feeding animals with a quantity of CSA molecules can, insome cases, improve the health of the animals. By way of example, CSAmolecules, when ingested by an animal, may provide one or more of thefollowing benefits: (1) reduced harmful bacteria in a digestive tract ofthe animal; (2) increased beneficial bacteria flora in the digestivetract of the animal; (3) improved feed conversion efficiency by theanimal; (4) reduced morbity of the animal; (5) reduced mortality of theanimal; or (6) harvested meat from the animal having a reduced contentof harmful bacteria.

In some embodiments, the water delivery system provides drinking waterto humans. The water delivery system may comprise a water storage vesselor well and one or more water lines in fluid communication with thewater storage vessel or well that are configured to transport or deliverwater to one or more locations, such as house or buildings. The one ormore water lines may comprise a plurality of pipes or conduits, such aspipes or conduits made of metal or polymers.

In addition to cleaning or disinfecting the water delivery system, suchas by killing microbes and/or breaking up biofilms, the CSA moleculesmay also form complexes with metal ions, metal compounds, orcontaminants in water passing through the water delivery line. In someembodiments, it may be desirable to remove at least a portion of the CSAmolecules or CSA complexes in culinary water prior to ingestion byhumans, such as by filtration systems and methods known in the art.

IV. Water Deliver Systems

Water delivery systems for use with the disclosed methods and/or whichare self-cleaning or self-disinfecting include structures known in thearts and/or means for performing the disclosed methods and/or methodsteps.

Example water delivery systems may include one or more water storagevessels having a capacity of at least 1 liter, 5 liters, 10 liters, 50liters, 100 liters, 500 liters, 1000 liters, 5000 liters, 10,000 liters,100,000 liters, or 1,000,000 liters. The water delivery systems mayinclude one or more water delivery lines having a length of at least 0.5meter, 1 meter, 5 meters, 10 meters, 25 meters, 50 meters, 100 meters,1000 meters, 5 kilometers, 10 kilometers, or 100 kilometers. The waterstorage vessels and/or water delivery lines may have walls constructedfrom one or more materials selected from metals, wood, polymers,composites, concrete, or ceramics.

Water delivery systems can be used to deliver water for many differentuses, including, but not limited to, culinary uses and industrial uses.Water delivery systems exclude dental unit water lines and other tubingand connection products that form a part of, or an integral connectionto, a medical device (such as dialysate delivery systems and waterpurifications systems for hemodialysis).

Referring now to the drawings, FIG. 1 schematically illustrates a watercleaning or disinfecting system 100 for use in cleaning or disinfectinga water delivery line 102. Water delivery line 102 may be used for anydesired purpose, such as for delivering water 104 to a water storagevessel 106, which may be used to provide drinking water to an animal orhuman. CSA molecules added to water delivery line 102 and/or waterstorage vessel 106 may advantageously kill microbes and/or break upbiofilms that may be present within water delivery line 102 and/or waterstorage vessel 106. A water storage vessel or well (not shown) can bepositioned upstream from water delivery line 102 in order to provide asource of water passing through water delivery line 102.

A CSA dispensing vessel 110 is positioned upstream from water deliveryline 102 and can be configured to provide a metered quantity of CSAmolecules to water passing through water delivery line 102. A conduit112 fluidly couples dispensing vessel 110 with water delivery line 102.The CSA dispensing vessel 110 may include a concentrated CSAcomposition, such as an aqueous or other liquid CSA containingcomposition. A metering pump 114 positioned along or in fluidcommunication with conduit 112 can be configures to provide a meteredquantity of CSA composition to water delivery line 102. A valve 116positioned along conduit 112 can be selectively opened or closed inorder to periodically provide CSA composition to water delivery line 102and/or provide a desired quantity of CSA composition.

For example, it may be desirable to periodically flush water deliveryline 102 with a relatively high concentration of CSA molecules in orderto rapidly clean or disinfect water delivery line 102 and/or waterstorage vessel 106. Thereafter, a smaller concentration of CSA moleculesor water without CSA molecules can be periodically passed through waterdelivery line 102 in order to provide drinking water to humans oranimals that contain no CSA molecules or a smaller concentration of CSAmolecules.

FIG. 2 schematically illustrates a water cleaning or disinfecting system200 for use in cleaning or disinfecting a water storage vessel 214and/or one or more water delivery lines 216 in fluid communication withwater storage vessel 214. A CSA dispensing vessel 210 positionedupstream from water storage vessel 214 is configured to provide aconstant and/or metered quantity of CSA molecules via one or moreconduits 212 to water storage vessel 214. For example, a plurality ofconduits 212 a and 212 b may be individually actuated as desired tocontrol the amount of CSA composition or molecules delivered to waterstorage vessel 214. For example, conduits 212 a and 212 b may providedifferent flow rates and/or concentrations of CSA molecules.

A plurality of water delivery lines, such as illustrated lines 216 a,216 b, and 216 c, can be used to transport or deliver water from waterstorage vessel 214 to different locations, such as houses, buildings, orconfined animal feed operations. CSA molecules added to water storagevessel 214 may advantageously kill microbes and/or break up biofilmsthat may be present within water storage vessel 214 and/or waterdelivery lines 216 and/or water storage vessels (not shown) downstreamfrom water delivery lines 216.

FIG. 3 schematically illustrates a CSA-releasing insert 300 that may bepositioned within and/or form part of a water delivery system, such aswithin or part of a water storage vessel or water delivery line.CSA-releasing insert 300 includes an insert substrate 302, which isformed from an appropriate CSA-eluting polymer or material, and CSAmolecules 304 impregnated within insert substrate 302. The CSA-elutingpolymer or material of insert substrate 302 is configured to release CSAmolecules into water or other liquid in contact with insert 300. In someembodiments, insert substrate 302 may be sized and configured fortemporary attachment to an interior surface or region of a water storagevessel or water delivery line. CSA-releasing insert 300 may comprise apipe configured to temporarily or permanently form part of a waterdelivery line or water storage vessel. If CSA-releasing insert 300becomes spent and no longer releases a desired minimum quantity of CSAmolecules, it can be augmented or replaced within another CSA-releasinginsert 300.

FIG. 4 schematically illustrates a CSA-releasing insert 400 that may bepositioned within and/or form part of a water delivery system, such aswithin or part of a water storage vessel or water delivery line.CSA-releasing insert 400 includes an insert substrate 402, which isformed from an appropriate polymer or other material, and a CSA-elutingcomposition 404 coated on a surface of insert substrate 402. CSA-elutingcomposition 404 is configured to release CSA molecules into water orother liquid in contact with insert 400. In some embodiments, insert 402may be sized and configured for temporary attachment to an interiorsurface or region of a water storage vessel or water delivery line.CSA-releasing insert 400 may comprise a pipe configured to temporarilyor permanently form part of a water delivery line or water storagevessel. If the CSA-releasing insert becomes spent and no longer releasesa desired minimum quantity of CSA molecules, it can be augmented orreplaced within another CSA-releasing insert.

The present invention may be embodied in other specific forms withoutdeparting from its spirit or essential characteristics. The describedembodiments are to be considered in all respects only as illustrativeand not restrictive. The scope of the invention is, therefore, indicatedby the appended claims rather than by the foregoing description. Allchanges which come within the meaning and range of equivalency of theclaims are to be embraced within their scope.

What is claimed is:
 1. A method for cleaning or disinfecting a waterdelivery line, comprising: adding cationic steroidal antimicrobial (CSA)molecules to water to form an aqueous CSA composition; and passing theaqueous CSA composition through the water delivery line.
 2. A method asin claim 1, wherein the water delivery line provides drinking water toanimals.
 3. A method as in claim 2, wherein the water delivery lineprovides drinking water to at least one of cattle, horses, sheep, swine,or poultry.
 4. A method as in claim 2, wherein the water delivery lineprovides drinking water to at least one of turkeys or chickens.
 5. Amethod as in claim 2, wherein the drinking water provides a quantity ofCSA molecules in order to improve the health of the animals.
 6. A methodas in claim 1, wherein the water delivery line provides drinking waterto humans.
 7. A method as in claim 1, wherein the aqueous CSAcomposition breaks up biofilms within the water delivery line.
 8. Amethod as in claim 1, wherein the CSA molecules form complexes withmetal ions or metal compounds in water passing through the waterdelivery line.
 9. A method as in claim 1, further comprising combiningthe CSA molecules with a liquid or solid to form a CSA deliverycomposition and contacting the CSA delivery composition with water inthe water delivery line to form the aqueous CSA composition.
 10. Amethod as in claim 1, wherein the water delivery line forms part of awater delivery system comprised of a water storage vessel or well andone or more water lines in fluid communication with the water storagevessel or well that transport water to one or more locations.
 11. Amethod as in claim 10, wherein the one or more water lines comprise aplurality of pipes or conduits.
 12. A method as in claim 11, wherein thepipes or conduits are made of metal.
 13. A method as in claim 10,wherein the CSA molecules are added to water in the storage vessel orwell.
 14. A method as in claim 10, further comprising mixing the CSAmolecules with water to form a concentrated CSA composition andintroducing the concentrated CSA composition into at least one of thestorage vessel, well, or one or more water lines.
 15. A method as inclaim 1, wherein the aqueous CSA composition is periodically passedthrough the water delivery line, and wherein water without the CSAmolecules is periodically passed through the water delivery line.
 16. Amethod as in claim 1, further comprising applying a CSA-elutingcomposition to an interior surface of the water delivery line, theCSA-eluting composition releasing at least a portion of the CSAmolecules added to the water to form the aqueous CSA composition.
 17. Amethod as in claim 1, further comprising applying a CSA-elutingcomposition to an interior surface of a water storage vessel upstreamfrom the water delivery line, the CSA-eluting composition releasing atleast a portion of the CSA molecules added to the water to form theaqueous CSA composition.
 18. A method as in claim 1, wherein at least aportion of the CSA molecules are provided by a CSA-containing tablet,powder, or eluting device.
 19. A method as in claim 18, the methodcomprising placing the CSA-containing tablet, powder, or eluting deviceinto a storage vessel upstream from the water delivery line.
 20. Amethod as in claim 1, wherein the water delivery line has a length of atleast 1 meter, 5 meters, 10 meters, 25 meters, 50 meters, 100 meters,1000 meters, or 5 kilometers.
 21. A method as in claim 1, wherein thewater delivery system comprises a water storage vessel having a capacityof at least 10 liters, 50 liters, 100 liters, 500 liters, 1000 liters,5000 liters, 10,000 liters, or 100,000 liters.
 22. A method as in claim1, wherein the water delivery system comprises at least one waterstorage vessel of a confined animal feed operation.
 23. A method as inclaim 1, wherein the water delivery system comprises at least one waterstorage vessel that provides drinking water to at least one of a house,building, or human.
 24. A method for cleaning or disinfecting a waterdelivery line that delivers drinking water to animals, comprising:adding cationic steroidal antimicrobial (CSA) molecules to the waterdelivery line to form an aqueous CSA composition; and passing theaqueous CSA composition through the water delivery line.
 25. A method asin claim 24, further comprising introducing water from the waterdelivery line to a drinking trough or vessel from which one or moreanimals drink.
 26. A method as in claim 24, wherein the aqueous CSAcomposition provides a quantity of CSA molecules that, when ingested bythe animals, improves the health of the animals.
 27. A method as inclaim 24, wherein the animals are located in a confined animal feedoperation.
 28. A method as in claim 24, wherein the animals are selectedfrom the group of cattle, horses, sheep, swine, poultry, andcombinations thereof.
 29. A method as in claim 24, wherein the CSAmolecules provide at least one of the following: reduced harmfulbacteria in a digestive tract of an animal; increased beneficialbacteria flora in the digestive tract of the animal; improved feedconversion efficiency by the animal; reduced morbity of the animal;reduced mortality of the animal; or harvested meat from the animalhaving a reduced content of harmful bacteria.
 30. A method for cleaningor disinfecting a water delivery system comprised of a water storagevessel or well and a water delivery line in fluid communication with thewater storage vessel or well, comprising: adding cationic steroidalantimicrobial (CSA) molecules to water to form an aqueous CSAcomposition; and passing the aqueous CSA composition through at leastone of the water delivery line or water storage vessel.
 31. A method asin claim 30, wherein the water delivery system provides drinking waterto animals or humans.
 32. A method as in claim 30, wherein the waterdelivery system is configured to deliver water to houses and buildings.33. A method as in claim 30, wherein the water delivery system comprisesthe well, and wherein adding the CSA molecules to water to form theaqueous CSA composition comprises introducing the CSA molecules into thewell.
 34. A method as in claim 30, wherein adding the CSA molecules towater to form the aqueous CSA composition comprises introducing the CSAmolecules into the water storage vessel.
 35. A method as in claim 34,wherein the water storage vessel comprises a drinking trough or vesselfrom which one or more animals drink.
 36. A method as in claim 35,wherein the one or more animals are located in a confined animal feedoperation.
 37. A method as in claim 35, wherein the one or more animalsare selected from the group of cattle, horses, sheep, swine, poultry,and combinations thereof.
 38. A self-cleaning or self-disinfecting waterdelivery system, comprising: at least one of a water delivery line or awater storage vessel; and a CSA-eluting composition on an interiorsurface of the water delivery line and/or within the water storagevessel, wherein the CSA-eluting composition is formulated to release CSAmolecules into water in the water delivery line and/or water storagevessel.
 39. A self-cleaning or self-disinfecting water delivery systemas in claim 38, wherein the CSA-eluting composition comprises aCSA-eluting composition on an interior surface of the water deliveryline and/or water storage vessel.
 40. A self-cleaning orself-disinfecting water delivery system as in claim 38, wherein theCSA-eluting composition comprises a CSA-releasing table, CSA-releasingpowder, or CSA-eluting device.
 41. A self-cleaning or self-disinfectingwater delivery system as in claim 38, wherein the water delivery systemincludes one or more water tanks positionable upstream of one or morewater lines.
 42. A self-cleaning or self-disinfecting water deliverysystem as in claim 38, wherein the water storage vessel is an animaldrinking trough or vessel.
 43. A self-cleaning or self-disinfectingwater delivery system as in claim 38, wherein the water storage vesselis configured to provide drinking water to one or more animals in aconfined animal feed operation.
 44. A self-cleaning or self-disinfectingwater delivery system as in claim 38, wherein the water storage vesselis configured to provide drinking water to one or more of cattle,horses, sheep, swine, or poultry.
 45. A CSA-releasing insert forattachment to and cleaning or disinfecting of a water delivery system,comprising: an insert substrate for placement on or within a waterstorage vessel or water delivery line; and a CSA-eluting composition ona surface of or impregnated in the insert substrate, wherein theCSA-eluting composition is formulated to release CSA molecules intowater within a water storage vessel or water delivery line.
 46. ACSA-releasing insert as in claim 45, wherein the insert comprises a pipeconfigured to temporarily or permanently form part of the water deliveryline.
 47. A CSA-releasing insert as in claim 45, wherein the insertsubstrate is sized and configured for attachment to an interior surfaceor region of the water storage vessel or water delivery line.
 48. Amethod, system, or insert as in any one of claim 1, 24, 29, 38, or 45,wherein the cationic steroidal antimicrobial (CSA) molecules include oneor more compounds according to Formula (I), or a salt thereof:

wherein rings A, B, C, and D are independently saturated, or are fullyor partially unsaturated, provided that at least two of rings A, B, C,and D are saturated; m, n, p, and q are independently 0 or 1; R₁-R₁₈ aresubstituent groups attached to one of rings A, B, C, or D; whereinR₁-R₁₈ are independently selected from the group consisting of hydrogen,hydroxyl, a substituted or unsubstituted alkyl, a substituted orunsubstituted hydroxyalkyl, a substituted or unsubstitutedalkyloxyalkyl, a substituted or unsubstituted alkylcarboxyalkyl, asubstituted or unsubstituted alkylaminoalkyl, a substituted orunsubstituted alkylaminoalkylamino, a substituted or unsubstitutedalkylaminoalkylaminoalkylamino, a substituted or unsubstitutedaminoalkyl, a substituted or unsubstituted aryl, a substituted orunsubstituted arylaminoalkyl, a substituted or unsubstituted haloalkyl,a substituted or unsubstituted alkenyl, a substituted or unsubstitutedalkynyl, oxo, a linking group attached to a second steroid, asubstituted or unsubstituted aminoalkyloxy, a substituted orunsubstituted aminoalkyloxyalkyl, a substituted or unsubstitutedaminoalkylcarboxy, a substituted or unsubstitutedaminoalkylaminocarbonyl, a substituted or unsubstitutedaminoalkylcarboxamido, a substituted or unsubstituteddi(alkyl)aminoalkyl, a substituted or unsubstituted C-carboxyalkyl;H₂N—HC(Q₅)-C(O)—O—, H₂NHC(Q₅)-C(O)—N(H)—, a substituted or unsubstitutedazidoalkyloxy, a substituted or unsubstituted cyanoalkyloxy,P.G.-HN—HC(Q₅)-C(O)—O—, a substituted or unsubstitutedguanidinoalkyloxy, a substituted or unsubstituted quaternary ammoniumalkylcarboxy, and a substituted or unsubstituted guanidinoalkyl carboxy,where Q₅ is a side chain of an amino acid, and P.G. is an aminoprotecting group
 49. A method, system, or insert as in claim 48,wherein: R₁ through R₄, R₆, R₇, R₁₁, R₁₂, R₁₅, R₁₆, and R₁₈ areindependently selected from the group consisting of hydrogen, hydroxyl,a substituted or unsubstituted alkyl, a substituted or unsubstitutedhydroxyalkyl, a substituted or unsubstituted alkyloxyalkyl, asubstituted or unsubstituted alkylcarboxyalkyl, a substituted orunsubstituted alkylaminoalkyl, a substituted or unsubstitutedalkylaminoalkylamino, a substituted or unsubstitutedalkylaminoalkylaminoalkylamino, a substituted or unsubstitutedaminoalkyl, a substituted or unsubstituted aryl, a substituted orunsubstituted arylaminoalkyl, a substituted or unsubstituted haloalkyl,a substituted or unsubstituted alkenyl, a substituted or unsubstitutedalkynyl, oxo, a linking group attached to a second steroid, asubstituted or unsubstituted aminoalkyloxy, a substituted orunsubstituted aminoalkyloxyalkyl, a substituted or unsubstitutedaminoalkylcarboxy, a substituted or unsubstitutedaminoalkylaminocarbonyl, a substituted or unsubstitutedaminoalkylcarboxamido, a substituted or unsubstituteddi(alkyl)aminoalkyl, H₂N—HC(Q₅)-C(O)—O—, H₂N—HC(Q₅)-C(O)—N(H)—, asubstituted or unsubstituted azidoalkyloxy, a substituted orunsubstituted cyanoalkyloxy, P.G.-HN—HC(Q₅)-C(O)—O—, a substituted orunsubstituted guanidinoalkyloxy, a substituted or unsubstitutedquaternary ammonium alkylcarboxy, and a substituted or unsubstitutedguanidinoalkyl carboxy, where Q₅ is a side chain of an amino acid, andP.G. is an amino protecting group; and R₅, R₈, R₉, R₁₀, R₁₃, R₁₄ and R₁₇are independently deleted when one of rings A, B, C, or D is unsaturatedso as to complete the valency of the carbon atom at that site, or R₅,R₈, R₉, R₁₀, R₁₃, and R₁₄ are independently selected from the groupconsisting of hydrogen, hydroxyl, a substituted or unsubstituted alkyl,a substituted or unsubstituted hydroxyalkyl, a substituted orunsubstituted alkyloxyalkyl, a substituted or unsubstituted aminoalkyl,a substituted or unsubstituted aryl, a substituted or unsubstitutedhaloalkyl, a substituted or unsubstituted alkenyl, a substituted orunsubstituted alkynyl, oxo, a linking group attached to a secondsteroid, a substituted or unsubstituted aminoalkyloxy, a substituted orunsubstituted aminoalkylcarboxy, a substituted or unsubstitutedaminoalkylaminocarbonyl, a substituted or unsubstituteddi(alkyl)aminoalkyl, H₂N—HC(Q₅)-C(O)—O—, H₂N—HC(Q₅)-C(O)—N(H)—,azidoalkyloxy, cyanoalkyloxy, P.G.-HN—HC(Q₅)-C(O)—O—, guanidinoalkyloxy,and guanidinoalkylcarboxy, where Q₅ is a side chain of an amino acid,P.G. is an amino protecting group, provided that at least two of R₁₋₄,R₆, R₇, R₁₁, R₁₂, R₁₅, R₁₆, R₁₇, and R₁₈ are independently selected fromthe group consisting of a substituted or unsubstituted aminoalkyl, asubstituted or unsubstituted aminoalkyloxy, a substituted orunsubstituted alkylcarboxyalkyl, a substituted or unsubstitutedalkylaminoalkylamino, a substituted or unsubstitutedalkylaminoalkylaminoalkylamino, a substituted or unsubstitutedaminoalkylcarboxy, a substituted or unsubstituted arylaminoalkyl, asubstituted or unsubstituted aminoalkyloxyaminoalkylaminocarbonyl, asubstituted or unsubstituted aminoalkylaminocarbonyl, a substituted orunsubstituted aminoalkylcarboxyamido, a quaternary ammoniumalkylcarboxy, a substituted or unsubstituted di(alkyl)aminoalkyl,H₂N—HC(Q₅)-C(O)—O—, H₂N—HC(Q₅)-C(O)—N(H)—, azidoalkyloxy, cyanoalkyloxy,P.G.-HN—HC(Q₅)-C(O)—O—, a substituted or unsubstitutedguanidinoalkyloxy, and a substituted or unsubstitutedguanidinoalkylcarboxy.
 50. A method, system, or insert as in claim 48,wherein R₁ through R₄, R₆, R₇, R₁₁, R₁₂, R₁₅, R₁₆, and R₁₈ areindependently selected from the group consisting of hydrogen, hydroxyl,a substituted or unsubstituted (C₁-C₁₈) alkyl, a substituted orunsubstituted (C₁-C₁₈) hydroxyalkyl, a substituted or unsubstituted(C₁-C₁₈) alkyloxy-(C₁-C₁₈) alkyl, a substituted or unsubstituted(C₁-C₁₈) alkylcarboxy-(C₁-C₁₈) alkyl, a substituted or unsubstituted(C₁-C₁₈) alkylamino-(C₁-C₁₈)alkyl, a substituted or unsubstituted(C₁-C₁₈) alkylamino-(C₁-C₁₈) alkylamino, a substituted or unsubstituted(C₁-C₁₈) alkylamino-(C₁-C₁₈) alkylamino-(C₁-C₁₈) alkylamino, asubstituted or unsubstituted (C₁-C₁₈) aminoalkyl, a substituted orunsubstituted aryl, a substituted or unsubstituted arylamino-(C₁-C₁₈)alkyl, a substituted or unsubstituted (C₁-C₁₈) haloalkyl, a substitutedor unsubstituted C₂-C₆ alkenyl, a substituted or unsubstituted C₂-C₆alkynyl, oxo, a linking group attached to a second steroid, asubstituted or unsubstituted (C₁-C₁₈) aminoalkyloxy, a substituted orunsubstituted (C₁-C₁₈) aminoalkyloxy-(C₁-C₁₈) alkyl, a substituted orunsubstituted (C₁-C₁₈) aminoalkylcarboxy, a substituted or unsubstituted(C₁-C₁₈) aminoalkylaminocarbonyl, a substituted or unsubstituted(C₁-C₁₈) aminoalkylcarboxamido, a substituted or unsubstituted di(C₁-C₁₈alkyl)aminoalkyl, H₂N—HC(Q₅)-C(O)—O—, H₂N—HC(Q₅)-C(O)—N(H)—, asubstituted or unsubstituted (C₁-C₁₈) azidoalkyloxy, a substituted orunsubstituted (C₁-C₁₈) cyanoalkyloxy, P.G.-HN—HC(Q₅)-C(O)—O—, asubstituted or unsubstituted (C₁-C₁₈) guanidinoalkyloxy, a substitutedor unsubstituted (C₁-C₁₈) quaternaryammoniumalkylcarboxy, and asubstituted or unsubstituted (C₁-C₁₈) guanidinoalkyl carboxy, where Q₅is a side chain of an amino acid, and P.G. is an amino protecting group;R₅, R₈, R₉, R₁₀, R₁₃, R₁₄ and R₁₇ are independently deleted when one ofrings A, B, C, or D is unsaturated so as to complete the valency of thecarbon atom at that site, or R₅, R₈, R₉, R₁₀, R₁₃, and R₁₄ areindependently selected from the group consisting of hydrogen, hydroxyl,a substituted or unsubstituted (C₁-C₁₈) alkyl, a substituted orunsubstituted (C₁-C₁₈) hydroxyalkyl, a substituted or unsubstituted(C₁-C₁₈) alkyloxy-(C₁-C₁₈) alkyl, a substituted or unsubstituted(C₁-C₁₈) aminoalkyl, a substituted or unsubstituted aryl, a substitutedor unsubstituted (C₁-C₁₈) haloalkyl, a substituted or unsubstituted(C₂-C₆) alkenyl, a substituted or unsubstituted (C₂-C₆) alkynyl, oxo, alinking group attached to a second steroid, a substituted orunsubstituted (C₁-C₁₈) aminoalkyloxy, a substituted or unsubstituted(C₁-C₁₈) aminoalkylcarboxy, a substituted or unsubstituted (C₁-C₁₈)aminoalkylaminocarbonyl, a substituted or unsubstituted di(C₁-C₁₈alkyl)aminoalkyl, H_(2N)—HC(Q₅)—C(O)—O—, H₂N—HC(Q₅)-C(O)—N(H)—, asubstituted or unsubstituted (C₁-C₁₈) azidoalkyloxy, a substituted orunsubstituted (C₁-C₁₈) cyanoalkyloxy, P.G.-HN—HC(Q₅)-C(O)—O—, asubstituted or unsubstituted (C₁-C₁₈) guanidinoalkyloxy, and (C₁-C₁₈)guanidinoalkylcarboxy, where Q₅ is a side chain of an amino acid, andP.G. is an amino protecting group; provided that at least three of R₁₋₄,R₆, R₇, R₁₁, R₁₂, R₁₅, R₁₆, R₁₇, and R₁₈ are independently selected fromthe group consisting of a substituted or unsubstituted (C₁-C₁₈)aminoalkyl, a substituted or unsubstituted (C₁-C₁₈) aminoalkyloxy, asubstituted or unsubstituted (C₁-C₁₈) alkylcarboxy-(C₁-C₁₈) alkyl, asubstituted or unsubstituted (C₁-C₁₈) alkylamino-(C₁-C₁₈) alkylamino, asubstituted or unsubstituted (C₁-C₁₈) alkylamino-(C₁-C₁₈) alkylamino(C₁-C₁₈) alkylamino, a substituted or unsubstituted (C₁-C₁₈)aminoalkylcarboxy, a substituted or unsubstituted arylamino (C₁-C₁₈)alkyl, a substituted or unsubstituted (C₁-C₁₈) aminoalkyloxy (C₁-C₁₈)aminoalkylaminocarbonyl, a substituted or unsubstituted (C₁-C₁₈)aminoalkylaminocarbonyl, a substituted or unsubstituted (C₁-C₁₈)aminoalkylcarboxyamido, a substituted or unsubstituted (C₁-C₁₈)quaternaryammoniumalkylcarboxy, a substituted or unsubstituted di(C₁-C₁₈alkyl)aminoalkyl, H₂N—HC(Q₅)-C(O)—O—, H₂N—HC(Q₅)-C(O)—N(H)—, asubstituted or unsubstituted (C₁-C₁₈) azidoalkyloxy, a substituted orunsubstituted (C₁-C₁₈) cyanoalkyloxy, P.G.-HN—HC(Q₅)-C(O)—O—, asubstituted or unsubstituted (C₁-C₁₈) guanidinoalkyloxy, and asubstituted or unsubstituted (C₁-C₁₈) guanidinoalkylcarboxy.
 51. Amethod, system, or insert as in claim 48, wherein the one or morecompounds of Formula (I) or salt thereof comprise a compound of Formula(IB):


52. A method, system, or insert as in claim 51, wherein R₃, R₇, and R₁₂are each independently aminoalkyloxy or aminoalkylcarboxy.
 53. A method,system, or insert as in claim 52, wherein R₁₈ is selected from the groupconsisting of: alkylaminoalkyl, di(alkyl)aminoalkyl,alkoxycarbonylalkyl, alkylcarboxyalkyl, and C-carboxyalkyl.
 54. Amethod, system, or insert as in claim 48, wherein the CSA molecules areselected from the group consisting of:

and salts thereof.